Due to the generally improved health situation in the western world, elderly-related diseases are much more common now than in the past and are likely to be even more common in the future.
One of the elderly-related symptoms is a reduction of the cognitive functions. This symptom is especially pronounced in the pathophysiological disease known as Alzheimer's disease. This disease is combined with, and also most likely caused by, an up to 90% degeneration of the cholinergic neurons in nucleus basalis, which is part of substantia innominata. These neurons project to the prefrontal cortex and hippocampus and have a general stimulatory effect on the cognitive functions of the forebrain as well as of hippocampus, namely learning, association, consolidation, and recognition.
It is a characteristic of Alzheimer's disease that although the cholinergic neurons degenerate, the postsynaptic receptors in the forebrain and hippocampus still exist. Therefore cholinergic agonists are useful in the treatment of Alzheimer's disease, in halting progression of Alzheimer's disease, and in improving the cognitive functions of elderly people.
Compounds active at a muscarinic cholinergic receptor are also useful analgesic agents and therefore are useful in the treatment of severely painful conditions.
Furthermore, the compounds of this invention are useful in the treatment of glaucoma, psychosis, mania, bipolar disorder, schizophrenia or schizophreniform conditions, depression, bladder dysfunctions, anxiety, sleeping disorders, epilepsy, cerebral ischemia and gastrointestinal motility disorders.
WO 92/03433 and WO 94/20496 disclose therapeutically active azabicyclic compounds which are substituted by either a 1,2,5-thiadiazole or a 1,2,5-oxadiazole ring system. The compounds disclosed therein are active at the muscarinic cholinergic receptors.
Within the muscarinic cholinergic pharmacology five subtypes of muscarinic cholinergic receptors exist which are M.sub.1 through M.sub.5. Some muscarinic cholinergic receptor active compounds are associated with side effects attributed to undesired modulation of the muscarinic cholinergic receptors.
Therefore, new compounds having muscarinic cholinergic activity are desired which have a better combination of receptor subtype efficacy, potency and selectivity.
The presently claimed compounds have a surprisingly good combination of M.sub.1 receptor efficacy, potency and selectivity.